AntibioticResistance in a Diabetic Patient

AntibioticResistance in a Diabetic Patient

Staphylococcusaureusis the primary bacterial cause of soft tissue, skin and boneinfections. Some of the general features of Staphylococcusaureusinclude non-motility, non-spore forming, most strains arefacultative anaerobes (S.aureusanaerobiusbeingthe only exception). Most of the strains produce different types oftoxins such as exfoliative toxins, enterotoxins and the toxic shocksyndrome toxin (TSST-1). Growth parameters for S.aureusstrains vary depending on various factors such as temperature, pH,water activity and presence of oxygen. More or more strains is foundin healthy people at any given time however the strains are usuallyasymptomatic. The problem is further worsened by the ability of theorganism to cause infection thereby colonizing the individual for alonger duration.

Spreadof the mutant strain depend on the accessibility of prone patients,and selective pressure employed via the use of antimicrobials,expanded possibility for transmission from bigger numbers of affectedpatients (“colonization strain”), and they have an impact onexecution and adherence to inhibition strategies. Patientssusceptible to colonization and illness comprise those with severeailments, chiefly those with compromised host defenses fromunderlying scientific stipulations surgery or indwelling clinicalitems. Hospitalized patients, primarily ICU patients, tend to be agreater danger as in comparison with non-hospitalized patients.

Theappropriate temperature for growth ranges between 7-48oCwith 37oCas the optimum temperature. The pH range is 4-10 with an optimumrange of 6-7 (Murray, Rosenthal, and Pfaller, 2015). The high-riskpopulation for healthcare-associated infections is patients currentlyon maintenance hemodialysis therapy (Eells etal.,2015). There is a higher risk for preceding infection in thispopulation due to the colonization of S.aureus.Hospitalized patients account for the majority of the strain whichhas been isolated and linked to VRSA. Some of the symptoms of VRSAinfection include reddish, warm skin in the area surrounding a woundin addition to drainage from the wound. Diagnosis is mainly throughblood tests or using samples such as urine or those obtained from awound.

Someof the predisposing factors to VRSA include the unreasonable use ofantibiotics more specifically over the counter prescriptions. Thishas a possibility of resulting in the elevated selective pressure ofvancomycin. Some clinical factors that play a significant role inincreasing the risk factor VRSA include vancomycin or glycopeptidesexposure, renal failure, and peritoneal dialysis. Treatment failurecontributes largely to the heteroresistant phenotype and may be thepioneer for glycopeptide resistance. Treatment of VRSA incorporatesvancomycin as one of the first-line drugs of choice. The constant useof this antibiotic for different infections for examplepseudomembranous colitis contributes to the selective drug strain.

Theinfrequent vancomycin-resistant Staphylococcusaureusstrains convey transposon Tn1546. Vancomycin-resistant Enterococcusfaecalis causethe derivation of these transposons which also lead to the change inthe metabolism and the cell wall structure. S.aureus,which contain Tn1546, are grouped into the clonal complex CC5, whichbelongs to the MRSA lineage.

Theimmoderate attraction of vancomycin to the d-alanyl-d-alanine depositelucidates the biochemical mechanism of the antibiotic. The residueis also considered to be a ubiquitous component of lipid II, a cellwall precursor. The d-alanyl-d-Lactate is the end product of theD-ala-D-ala, and this change plays a significant role in theestablishing resistance in the Tn1546 that eventually leads toantibiotic resistance (Gardete and Tomasz, 2014).

Someof the biochemical studies that have been conducted on MRSA strainCOL, which incorporates plasmid-borne copies of Tn1546 showed thepossibility of an equivalent but altered cell wall as elaborated instrains of VRE. The D-ala-D-lac plays a significant role in thereplacement of D-ala-D-ala terminal residues within the resistantbacterium. The mecA determinant is also present in this strain.

Curiously,the genetic factor fabricated from the mecA determinant with proteinsbinding to the penicillin component (PBP2A), a crucial aspect withregards to the staphylococcal resistance, more specifically β-lactamresistance. This made it difficult to utilize the cell wallprecursors after significant alterations. The synthesis andmodification of the D-ala-D-lactate pioneers within the cell wall wasonce catalyzed on this strain through the native penicillin-bindingprotein of S.aureus (Gardeteand Tomasz, 2014). These findings cited some measure of antagonism asnoted in the mecA-based and Tn1546-based resistance mechanisms.

Tofully grasp the mechanisms and effects of vancomycin resistance in S.aureus,there is a need to figure out how the organism acquires its cellwall. The staphylococcal cell wall plays an essential position in theprotection of cell wall integrity and additionally host-pathogeninteraction. A polysaccharide capsule covers the outer surface ofS.aureus.The cell wall is found in the capsule, and it comprises of cell walllinked proteins, cross-linked peptidoglycan layer in addition toteichoic acids. Vancomycin has been the choice of therapy since theemergence of methicillin-resistant S.aureus.Vancomycin inhibits biosynthesis of the late stage peptidoglycan andthis occurs outside the cytoplasmic membrane. Some hydrogen bondslink the d-Ala-d-Ala deposit to the peptide constituent ofvancomycin. Interference in the binding process between these twocomponents lowers the potency of the drug.

Diabeticwounds co-infected by resistant E.faecalisand MRSA have been identified to occur along with VRSA isolates.Another mechanism postulated for VRSA involves the exchange ofgenetic material. Co-infection of with MRSA and VRE among patientsplaces them at a higher risk for VRSA (Gardete and Tomasz, 2014).This leads to the possibility of transferring the vanA gene from VREto one of the elusive antibiotic strain, methicillin-resistantStaphylococcusaureusin a biofilm setting leading to VRSA strain. Conjugative transfer ofvanA gene is also possible in scenarios where resistant E.fecalisis isolated from the wound of a patient.

Onepossible mechanism for genetic transfer of antibiotic resistance fromone organism to the other involves the direct transfer of resistantgenes to bacterial progenies during the process of DNA replication.This is referred to as vertical gene transfer. A spontaneousalteration within the bacterial chromosome conveys resistance to amember of the bacterial populace (Loomba, Taneja, and Mishra, 2010).

Thisparticular patient would be at increased risk for infection with VRSAdue to the usage of vancomycin for the treatment of staphylococcalinfections. This leads to the possibility of increasing selectivepressure which leads to MRSA strains with a lower vulnerability tovancomycin. Treatment involves the use of agents through which VRSAis identified to be susceptible after conducting in vitro tests. Fewprescribed drugs are existing for VRSA treatment. Two of the more newantimicrobial agents presently on hand with action towardsdrug-resistant staphylococci include linezolid andQuinupristin-dalfopristin.

Isolateshave been known to develop resistance towards linezolid even thoughcross-resistance has not been observed during treatment. One of thedrugs currently undergoing trials is daptomycin which destroys thecytoplasmic membranes of organisms due to its bactericidal effects.Other modified agents are still currently in the development stagesand may take a while before they are introduced into the market. Someof these include oxazolidinones, glycopeptides, and carbapenems. Theonly way that can currently be used is avoiding the unreasonableusage of antibiotics in addition to creating coherent antibioticpolicies.


Eells,S. J., Kalantar-Zadeh, K., Bolaris, M. A., May, L., &amp Miller, L.G. (2015). Body site Staphylococcusaureuscolonization among maintenance hemodialysis patients. Nephron,129(2),79-83.

Gardete,S., and Tomasz, A. (2014). Mechanisms of vancomycin resistance inStaphylococcusaureus.TheJournal of clinical investigation,124(7),2836-2840. Retrieved from

Loomba,P. S., Taneja, J., and Mishra, B. (2010). Methicillin and vancomycinresistant S.aureusin hospitalized patients. Journalof global infectious diseases,2(3),275. Retrieved from

Murray,P. R., Rosenthal, K. S., &amp Pfaller, M. A. (2015). Medicalmicrobiology.Elsevier Health Sciences.